Our long-term immunologic studies of post-infectious fatigue disorders stimulated us to study immunologic responses to well-defined acute infections. To this end, we began two years ago to collaborate with investigators at the University of Virginia in Charlottesville who study influenza infection, its treatment, and prevention. They study patients in their community with naturally acquired influenza A virus infection and volunteers who are challenged with the virus. We developed assays for several human cytokines and measured their content in nasal secretions and plasma during and following acute infection. Cytokine levels are correlated with patient symptoms, fever, and virus shedding. Recently, we documented highly significant rises in local and systemic levels of interleukin-6 and TNF-alpha that correlate well with virus shedding and symptoms. We are now extending such studies as part of Phase I and II therapeutic trials of new neuraminidase inhibitor drugs for influenza. These studies indicate the nature and importance of immune responses in resolution of the infection and in symptom formation.